Multiple dosage injector with rack and pinion dosage system

ABSTRACT

A dispensing mechanism for delivering a dosage of medicament including a housing, a push button, a crank arm that is slideably engageable with the push button, a ram, and a ratchet gear releasably engageable with the crank arm and ram, translation of the push button along an axis causing the crank arm to engage and rotate the ratchet gear which causes the ram to distally advance relative to the housing.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/650,332 filed Jul. 14, 2017 which is a continuation of U.S. patentapplication Ser. No. 14/204,641 filed Mar. 11, 2014, now U.S. Pat. No.9,707,354, which claims priority of U.S. Provisional Patent ApplicationNo. 61/776,269 filed Mar. 11, 2013, each of which is incorporated byreference herein for all purposes.

FIELD OF THE DISCLOSURE

The present invention relates to an injection device capable ofdelivering multiple doses of a liquid medicament contained thereinwithout the need to refill the device between doses.

BACKGROUND

Various types of drug treatments, including hormone therapy and thelike, require administration of the drug-containing liquid medicament atregular intervals over an extended period of time. For example, aspecific hormone treatment can require daily administration of the drugfor a period of thirty days. In such a situation, it is advantageous toprovide a device that allows the patient to self-administer theinjection to avoid repeated trips to a doctor's office or the like.

A device is needed that allows for repeated administration of a dose ofmedicament that is easy to use correctly in self-administration.

SUMMARY

In one embodiment, the present invention is a dispensing mechanism,including a housing having a proximal-distal axis; a ram within thehousing and movable in a distal direction; a user-operable push buttonmoveable along the proximal-distal axis relative to the housing, thepush button including a slot at a distal portion of the push button; acrank arm having pawl tooth, a pivot point, and a crank arm protrusionslideably engageable with the slot such that movement of the push buttoncauses the crank arm protrusion to move along the slot, causing rotationof the crank arm about the pivot point; and a ratchet gear having afirst set of teeth releasably engageable with the pawl tooth and asecond set of teeth releaseably engageable with the ram, whereinengagement of the pawl tooth with the first set of teeth of the ratchetgear causes the ratchet gear to rotate, causing the ram to distallyadvance relative to the housing.

In another embodiment, the dispensing mechanism further includes ananti-reverse mechanism including at least one housing ratchet integrallyformed on an internal surface of the housing on both housing parts; anda flexible column integrally formed extending from a distal portion ofthe push button, the flexible column having a flexible column protrusionat a proximal end thereof, wherein as the push button moves along theproximal-distal axis, the flexible column protrusion slides between theintegrally formed ratchets on both housing parts and engages the housingratchets and restricts movement of the push button to one directionduring a resetting motion. In another embodiment, the flexible columnprotrusion is almond shaped and thicker than said column. In oneembodiment, having ratchets on both housing parts, the column slidingbetween them, and the almond engaging said ratchets allows the ratchetand column to be supported in a double shear type fashion furtherstrengthening and balancing applied loads on said mechanism. In oneembodiment, only one housing part contains an integrally formed ratchet,which makes the mechanism operate in single shear and tends to beunbalanced and weaker than other configurations.

In another embodiment, the ram includes at least two sets of teeth. Inone embodiment, a first set of ram teeth are configured to engage thesecond set of teeth of the ratchet gear, and a second set of ram teethare configured to engage a housing protrusion, the housing protrusionbeing integrally formed within the housing and configured to facilitatemovement of the ram in one direction. In another embodiment, the secondset of ratchet gear teeth are releasably engageable with a housingprotrusion being integrally formed within the housing and configured tofacilitate rotation of the gear in one direction.

In one embodiment, the push button slot is oriented at an oblique anglewith respect to the proximal-distal axis.

In one embodiment, the push button slot has a portion that is orientedat an oblique angle with respect to the proximal-distal axis and aportion that has varying angles to the proximal-distal axis.

In one embodiment, the invention is an injector including the dispensingmechanism; a cartridge disposed within the housing; a plunger disposedin the cartridge to seal a medicament therein, wherein the ram isassociated with the plunger for forcing the plunger in a distaldirection for ejecting a dose of medicament; and a needle in fluidcommunication with the cartridge for injecting the doses into a patient.In one embodiment, the medicament is administered at a fixed doserepetitively. In one embodiment, the medicament is administered invarying doses. In one embodiment, the medicament includes a parathyroidhormone. In another embodiment, the hormone is teriparatide. In oneembodiment, the medicament includes a glucagon-like peptide-1 agonist.In another embodiment, the glucagon-like peptide-1 agonist is exenatide.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other objects, features and advantages of the invention willbe apparent from a consideration of the following non-limiting detaileddescription considered in conjunction with the drawing figures, inwhich:

FIG. 1A is a side view of an injection device according to an exemplaryembodiment of the present disclosure;

FIG. 1B is a cross-sectional rear side view of the injection deviceshown in FIG. 1A;

FIG. 1C is a cross-sectional front side view of the injection deviceshown in FIG. 1A;

FIG. 1D is a side partial view of an injection device according to anexemplary embodiment of the present disclosure;

FIG. 2A is a side view of a first portion of housing of the injectiondevice shown in FIG. 1A;

FIG. 2B is a side view of a second portion of housing of the injectiondevice shown in FIG. 1A;

FIG. 3A is a front side view of a dosage mechanism of the injectiondevice shown in FIG. 1A;

FIG. 3B is a rear side view of a dosage mechanism of the injectiondevice shown in FIG. 1A;

FIG. 4 is a side view of a ram of the injection device shown in FIG. 1A;

FIG. 5 is a side view of a ram and a second portion of housing of theinjection device shown in FIG. 1A;

FIG. 6 is a perspective view of a ratchet gear of the injection deviceshown in FIG. 1A;

FIG. 7 is a perspective view of a ratchet arm of the injection deviceshown in FIG. 1A;

FIG. 8 is a perspective view of a first exemplary user-manipulable pushbutton of the injection device shown in FIG. 1A;

FIGS. 9A, 9B, and 9C are side exploded views of a second exemplaryuser-manipulable push button of the injection device shown in FIG. 1D;

FIGS. 10A, 10B, and 10C are partial side cutaway views of the injectiondevice shown in FIG. 1D during operation;

FIGS. 11A, 11B, 11C, and 11D are a partial side cutaway views of theinjection device shown in FIG. 1D showing compression of an exemplaryforce limiting biasing member;

FIGS. 12A, 12B, 12C, 12D, and 12E are partial side cutaway views of ananti-reverse feature of the injection device shown in FIG. 1D;

FIGS. 13A, 13B, 13C, and 13D are partial side cutaway views of alock-out feature of the injection device shown in FIG. 1D;

FIG. 14A is a side view of the injection device shown in FIG. 1D;

FIG. 14B is a side view of the injection device shown in FIG. 1D;

FIG. 15A is a cross-sectional rear side view of the injection deviceshown in FIG. 1D;

FIG. 15B is a cross-sectional front side view of the injection deviceshown in FIG. 1D;

FIG. 16A is a side view of a first portion of housing of the injectiondevice shown in FIG. 1D;

FIG. 16B is a side view of a second portion of housing of the injectiondevice shown in FIG. 1D;

FIG. 17A is a front side view of a dosage mechanism of the injectiondevice shown in FIG. 1D;

FIG. 17B is a rear side view of a dosage mechanism of the injectiondevice shown in FIG. 1D;

FIG. 18 is a side view of a ram of the injection device shown in FIG.1D;

FIG. 19 is a side view of a ram and a second portion of housing of theinjection device shown in FIG. 1D;

FIG. 20 is a perspective view of a ratchet gear of the injection deviceshown in FIG. 1D; and

FIG. 21 is a perspective view of a ratchet arm of the injection deviceshown in FIG. 1D.

Throughout the drawings, the same reference numerals and characters,unless otherwise stated, are used to denote like features, elements,components, or portions of the illustrated embodiments. Moreover, whilethe present disclosure will now be described in detail with reference tothe figures, it is done so in connection with the illustrativeembodiments and is not limited by the particular embodiments illustratedin the figures.

DETAILED DESCRIPTION

With reference to the accompanying drawings, various embodiments of thepresent invention are described more fully below. Some but not allembodiments of the present invention are shown. Indeed, variousembodiments of the invention may be embodied in many different forms andshould not be construed as limited to the embodiments expresslydescribed. Like numbers refer to like elements throughout. The singularforms “a,” “an,” and “the” include the singular and plural unless thecontext clearly dictates otherwise.

Referring to the drawings in detail, wherein like reference numeralsindicate like elements throughout, there is shown in FIGS. 1-21 aninjection device 100, in accordance with an exemplary embodiment of thepresent invention. It is noted that, in the context of this disclosure,the terms “distal” and “proximal” are used in reference to the positionof injection device 100 relative to a user of the injection device whenmerely held by a user. Accordingly, a point located distal to a secondpoint would be further from the user (e.g., towards an injection end ofinjection device 100) and vice versa.

FIGS. 1A-1C and 2-8 show one embodiment of the present invention andFIGS. 1D and 9-21 show another embodiment of the present invention.

Referring to FIGS. 1A, 1B, 1C, 1D, 14A, 14B, 15A, and 15B, in certainembodiments, injection device 100 is configured to administer a dose ofmedicament. In one embodiment, injection device 100 is configured in theshape of a pen, having an elongated, substantially writinginstrument-like form, although other forms are within the scope of theinvention. Referring to FIGS. 14A and 14B, in one embodiment, injectiondevice 100 includes a removable cap 128 attached to the distal section122 of the injection device 100 thereto. In one embodiment, injectiondevice 100 is a disposable injection pen, in that after the quantity ofmedicament contained therein is exhausted by multiple operations of theinjection device 100, the injection device 100 is discarded rather thanbeing reset and re-used with a replacement container of medicament. Inother embodiments, injection device 100 can be reset and is reusable. Inone embodiment, the injection device 100 is a re-usable pen, and thatafter the quantity of medicament contained therein is exhausted, theinjection device can be re-set and a new medicament cartridge installed.

In one embodiment, injection device 100 is configured to administerrepeated, successive doses of a medicament. In one embodiment, themedicament is delivered in successive repeated fixed doses. In oneembodiment, the medicament is delivered in successive repeated variabledoses. In other embodiments, the dosage can be controlled and adjusted.Further, in one embodiment, injection device 100 allows the injection tobe administered by individuals that do not have formal training (e.g.,self-administered or administered by another individual family member orother caregiver who may not be a formally trained healthcare provider,such as a parent administering a drug to a child). In one embodiment,injection device 100 is triggered by one hand of a user. In oneembodiment, injection device 100 is held one hand of a user andtriggered by the user's finger or thumb. In one embodiment, injectiondevice 100 is useful in situations where self-injections/caregiveradministered injections would be beneficial, including, but not limitedto, the injection of a drug to treat osteoporosis, psoriasis, andpsoriatic arthritis. In one embodiment, the injection device mustadminister a full dose prior to being able to reset. In one embodiment,the injection device must fully reset before it is able to be triggered.

The injection device 100 can be used to inject a wide range of drugs.For example, injection device 100 can be used to inject drugs, watersoluble medicaments and oil soluble medicaments. Some medicaments thatcan be used with injector device 100 include parathyroid hormone (“PTH”)and various other medications such as exenatide and the like. Injectiondevice 100 can also be used to inject medicaments listed in thePhysicians' Desk Reference (PDR®), 67th Edition (2013) (which is hereinincorporated by reference in its entirety), and, without limitation,allergens, amebicides and trichomonacides, amino acid preparations,analeptic agents, analgesics, analgesics/antacids, anesthetics,anorexics, antacids, antihelmintics, antialcohol preparations,antiarthritics, antiasthma agents, antibacterials and antiseptics,antibiotics, antiviral antibiotics, anticancer preparations,anticholinergic drug inhibitors, anticoagulants, anticonvulsants,antidepressants, antidiabetic agents, antidiarrheals, antidiuretics,antienuresis agents, antifibrinolytic agents, antifibrotics (systemic),antiflatulents, antifungal agents, antigonadotropin, antihistamines,antihyperammonia agents, anti-inflammatory agents, antimalarials,antimetabolites, antimigraine preparations, antinauseants,antineoplastics, anti-obesity preparations, antiparasitics,anti-parkinsonism drugs, antipruritics, antipyretics, antispasmodics andanticholinergics, antitoxoplasmosis agents, antitussives, antivertigoagents, antiviral agents, apomorphine, atropine, biologicals,biosimilars, bismuth preparations, bone metabolism regulators, bowelevacuants, bronchial dilators, calcium preparations, cardiovascularpreparations, central nervous system stimulants, cerumenolytics,chelating agents, choleretics, cholesterol reducers andanti-hyperlipemics, colonic content acidifiers, cough and coldpreparations, decongestants, diazepam, dihydroergotamine, epinephrineexpectorants and combinations, diuretics, emetics, enzymes anddigestants, fertility agents, fluorine preparations, galactokineticagents, general anesthetic, geriatrics, germicides, glucagon,haloperidol, hematinics, hemorrhoidal preparations, histamine H receptorantagonists, hormones, hydrocholeretics, hyperglycemic agents,hypnotics, immunosuppressives, laxatives, lovenox, mucolytics, musclerelaxants, narcotic antagonists, narcotic detoxification agents,ophthalmological osmotic dehydrating agents, otic preparations,oxytocics, parashypatholytics, parathyroid preparations, pediculicides,peptide drugs, phosphorus preparations, premenstrual therapeutics,psychostimulants, quinidines, radiopharmaceuticals, respiratorystimulants, salt substitutes, scabicides, sclerosing agents, sedatives,sumatriptan, sympatholytics, sympathomimetics, thrombolytics, thyroidpreparations, toradol, tranquilizers, tuberculosis preparations,uricosuric agents, urinary acidifiers, urinary alkalinizing agents,urinary tract analgesic, urological irrigants, uterine contractants,vaginal therapeutics and vitamins and each specific compound orcomposition listed under each of the foregoing categories in the PDR®.Some other medicaments that can be used with injector device 100 includeErgocalciferol (Calciferol), diethylstilbestrol, Diprovan (propofol),estradiol valerate, fluphenazine decanoate, fulvestrant, intralipid,liposyn, nandrolone decanoate, nebido, nutralipid, paclitaxel,progesterone, prograf, testosterone cypionate, zuclopenthixol,haloperidol dodecanoate, Enbrel, Humira, Lantus, Epogen (Procrit),Neulasta, Aranesp, Avonex, PEGasys, Rebif, Neupogen, Betaseron, Avastin,Remicade, Herceptin, Erbitux, Recombinate, Cerezyme, NovoSeven, Tysabri,Synagis, Copaxone and Kogenate FS. In certain embodiments, themedicament is dissolved in soybean oil, ethyl oleate, castor oil, sesameoil, safflower oil, arachis oil, polyoxyethylated castor oil (Cremophor®EL), polyoxyl 60 hydrogenated castor oil (HCO-60), cottonseed oil, orthin oil derived from coconut oil.

In some embodiments, the medicament may be a hazardous agent. “HazardousAgent(s)” as used herein means any one or more medications that aretoxic agents, cytotoxic agents and/or other dangerous agents that maycause serious effects upon contact with a subject as well as highlypotent agents, agents that have profound physiological effects at lowdoses. Exemplary hazardous agents include, without limitation,analgesics, immunomodulating agents, IL-1 receptor antagonists, IL-2alpha receptor antagonists, anti-rejection compounds, hormonal agents,prostaglandins, sedatives, anticholinergic agents, Parkinsons diseasedrugs, expensive agents, neuroleptic agents, tissue necrosis factor(TNF) blockers, and other dangerous agents. Examples of hazardous agentssuitable for use with the injection device 100 in accordance with thepresent invention include, but are not limited to, those disclosed inU.S. Patent Application Publication No. 2012/0157965 entitled “HazardousAgent Injection System” (to Paul Wotton et. al, published Jun. 21,2012), which is incorporated by reference herein in its entirety.Particular examples of cytotoxic agents include, without limitation,6-mercaptopurine, 6-thioinosinic acid, azathioprine, chlorambucil,cyclophosphamide, cytophosphane, cytarabine, fluorouracil, melphalan,methotrexate, uramustine, anti-cytokine biologicals, cell receptorantagonists, cell receptor analogues, and derivatives thereof. Examplesof highly potent agents include, without limitation, steroids such asdexamethasone, progesterone, somatostatin, and analogues thereof;biologically active peptides such as teriparatide; and anticholinergicssuch as scopolamine. Examples of agents that have profound physiologicaleffects at low doses include, without limitation, antihypertensivesand/or blood pressure down regulators. Examples of analgesics include,without limitation, fentanyl, fentanyl citrate, morphine, meperidine,and other opioids. Examples of immunomodulating agents include, withoutlimitation, adalimumab (anti-tissue necrosis factor monoclonal antibodyor anti-TNF). Examples of IL-1 receptor antagonists include, withoutlimitation, anakinra. Examples of IL-2 alpha receptor antagonistsinclude, without limitation, daclizumab and basiliximab. Examples ofanti-rejection compounds include, without limitation, azathioprine,cyclosporine, and tacrolimus. Examples of hormonal agents include,without limitation, testosterone, estrogen, growth hormone, insulin,thyroid hormone, follicle stimulating hormone (FSH),epinephrine/adrenaline, progesterone, parathyroid hormone, gonadotrophinreleasing hormone (GHRH), leutinizing hormone releasing hormone (LHRH),other hormones such as those where contact with the hormone by membersof the opposite sex can lead to side effects, and derivatives thereof.Examples of prostaglandins include, without limitation, gamma-linolenicacid, docosahexanoic acid, arachidonic acid and eicosapentaenoic acid.Examples of sedatives include, without limitation, barbiturates such asamobarbital, pentobarbital, secobarbital, and phenobarbitol;benzodiazepines such as clonazepam, diazepam, estazolam, flunitrazepam,lorazepam, midazolam, nitrazepam, oxazepam, triazolam, temazepam,chlordiazepoxide, and alprazolam; herbal sedatives such as ashwagandha,duboisia hopwoodii, prosanthera striatiflora, kava (piper methysticum),mandrake, valerian, and marijuana; non-benzodiazepine sedatives (a.k.a.“Z-drugs”) such as eszopiclone, zaleplon, zolpidem, zopiclone;antihistamines such as diphenhydramine, dimenhydrinate, doxylamine, andpromethazine; and other sedatives such as chloral hydrate. Examples ofanticholinergic agents include, without limitation, dicyclomine,atropine, ipratropium bromide, oxitropium bromide, and tiotropium.Examples of Parkinson's disease drugs include, without limitation,levodopa, dopamine, carbidopa, benserazide, co-ceraldopa, co-beneldopa,tolcapone, entacapone, bromocriptine, pergolide, pramipexole,ropinirole, piribedil, cabergoline, apomorphine, and lisuride. Examplesof expensive agents include, without limitation, human growth hormoneand erythropoietin. Examples of neuroleptic agents includes, withoutlimitation, antipsychotics; butyrophenones such as haloperidol anddroperidol; phenothiazines such as chlorpromazine, fluphenazine,perphenazine, proclorperazine, thioridazine, trifluoperazine,mesoridazine, periciazine, promazine, triflupromazine, levomepromazine,promethazine, and pimozide; thioxanthenes such as chlorprothixene,clopenthixol, flupenthixol, thiothixene, and zuclopenthixol; atypicalantipsychotics such as clozapine, olanzapine, risperidone, quetiapine,ziprasidone, amisulpride, asenapine, paliperidone, iloperidone,zotepine, and sertindole; and third generation antipsychotics such asaripiprazole and bifeprunox. Examples of TNF blockers includes, withoutlimitation, etanercept.

In some embodiments, the hazardous agent can be selected from botulinumtoxin, injectable gold, 6-mercaptopurine, 6-thioinosinic acid,azathioprine, chlorambucil, cyclophosphamide, cytophosphane, cytarabine,fluorouracil, melphalan, methotrexate, uramustine, anti-cytokinebiologicals, cell receptor antagonists, cell receptor analogues,dexamethasone, progesterone, somatostatin, analogues of dexamethasone,analogues of progesterone, analogues of somatostatin, teriparatide,scopolamine, antihypertensives, blood pressure down regulators,fentanyl, fentanyl citrate, morphine, meperidine, other opioids,adalimumab (anti-tissue necrosis factor monoclonal antibody oranti-TNF), anakinra, daclizumab, basiliximab, azathioprine,cyclosporine, tacrolimus, testosterone, estrogen, growth hormone,insulin, thyroid hormone, follicle stimulating hormone (FSH),epinephrine/adrenaline, gamma-linolenic acid, docosahexanoic acid,arachidonic acid, eicosapentaenoic acid, amobarbital, pentobarbital,secobarbital, phenobarbitol, clonazepam, diazepam, estazolam,flunitrazepam, lorazepam, midazolam, nitrazepam, oxazepam, triazolam,temazepam, chlordiazepoxide, alprazolam, ashwagandha, duboisiahopwoodii, prosanthera striatiflora, kava (piper methysticum), mandrake,valerian, marijuana, eszopiclone, zaleplon, zolpidem, zopiclone,diphenhydramine, dimenhydrinate, doxylamine, promethazine, chloralhydrate, dicyclomine, atropine, ipratropium bromide, oxitropium bromide,tiotropium, levodopa, dopamine, carbidopa, benserazide, co-ceraldopa,co-beneldopa, tolcapone, entacapone, bromocriptine, pergolide,pramipexole, ropinirole, piribedil, cabergoline, apomorphine, lisuride,human growth hormone, erythropoietin, haloperidol, droperidol,chlorpromazine, fluphenazine, perphenazine, proclorperazine,thioridazine, trifluoperazine, mesoridazine, periciazine, promazine,triflupromazine, levomepromazine, promethazine, pimozide,chlorprothixene, clopenthixol, flupenthixol, thiothixene,zuclopenthixol, clozapine, olanzapine, risperidone, quetiapine,ziprasidone, amisulpride, asenapine, paliperidone, iloperidone,zotepine, sertindole, aripiprazole, bifeprunox, etanercept, derivativesof any of the foregoing, and combinations of any of the foregoing.

Because of the repeated nature of the dosing of certain types ofmedicaments, it is beneficial to use a device that aides a patient inself-administration of the doses. Repeat dosing includes repetitiveinjection of the same dose or variable dose. Medicaments that areadministered intradermally, subcutaneously or intramuscularly can beused with the injector. Further, many such medicaments should bedelivered in a precise amount to ensure efficacy and to reduceside-effects.

In one embodiment, the medicament includes a recombinant form ofparathyroid hormone, e.g., teriparatide. Teriparatide has the followingstructure:

Teriparatide is typically administered by injection once a day in thethigh or abdomen. Teriparatide is indicated for use in postmenopausalwomen with osteoporosis at a high risk for fracture or with a history ofosteoporotic fracture, patients with multiple risk factors for fracture,and for patients who have failed or are intolerant to other availableosteoporosis therapy. Teriparatide is also indicated to increase bonemass in men with primary or hypogonadal osteoporosis at high risk offracture, patients with multiple risk factors for fracture, and forpatients who have failed or are intolerant to other availableosteoporosis therapy. Teriparatide is indicated as well for thetreatment of men and women with osteoporosis associated with sustainedsystemic glucocorticoid therapy. The typical recommended dose is 20 μgper day. In one embodiment, injection device 100 is configured toadminister about 1 μg, about 2 μg, about 3 μg, about 4 μg, about 5 μg,about 6 μg, about 7 μg, about 8 μg, about 9 μg, about 10 μg, about 11μg, about 12 μg, about 13 μg, about 14 μg, 15 μg, about 16 μg, about 17μg, about 18 μg, about 19 μg, about 20 μg, about 21 μg, about 22 μg,about 23 μg, about 24 μg, about 25 μg, about 26 μg, about 27 μg, about28 μg, about 29 μg, about 30 μg, about 31 μg, about 32 μg, about 33 μg,about 34 μg, about 35 μg, about 36 μg, about 37 μg, about 38 μg, about39 μg, about 40 μg or any range determinable from the preceding dosageamounts (for example, about 15 μg to about 25 μg or about 1 μg to about10 μg) of medicament, e.g., Teriparatide, per dose. In one embodiment,injection device 100 is configured to administer about 0.005 mL, about0.010 mL, about 0.015 mL, about 0.020 mL, about 0.025 mL, about 0.030mL, about 0.035 mL, about 0.040 mL, about 0.045 mL, about 0.050 mL,about 0.055 mL, about 0.060 mL, about 0.065 mL, about 0.070 mL, 75 μL,about 0.080 mL, about 0.085 mL, about 0.090 mL, about 0.095 mL, about0.100 mL, about 0.105 mL, about 0.110 mL, about 0.115 mL, about 0.120mL, about 0.125 mL, about 0.130 mL or any range determinable from thepreceding dosage amounts (for example, about 0.025 mL to about 0.045 mLor about 0.005 mL to about 0.130 mL) of medicament, e.g., Teriparatide,per dose.

Referring to FIGS. 1A and 14A, in one embodiment, injection device 100includes a proximal section 120 and a distal section 122. In oneembodiment, distal section 122 contains the medicament to be dispensedat its distal end upon operation of injection device 100. In oneembodiment, the proximal section 120 contains the dosage mechanism 126,as shown in FIGS. 3A, 3B, 15A and 15B used to force the containedmedicament from the distal end of distal section 122.

In one embodiment, injection device 100 includes housing 102. In oneembodiment, housing 102 has a proximal-distal axis 124. In oneembodiment, housing 102 of injection device 100 is formed from a lightweight material, e.g., an injected molded plastic. In one embodiment,housing 102 is covered in an opaque or elastomeric covering to alter thecolor, shape or texture of housing 102. In one embodiment, housing 102is formed of at least two separate parts, e.g., first portion 1020 a andsecond portion 1020 b as shown in FIGS. 2A, 2B, 16A and 16B. In oneembodiment, the housing parts 1020 a and 1020 b are aligned via matingpins and recesses provided therein and fixedly secured together duringmanufacture, such as via adhesives or ultrasonic welding. In oneembodiment, the housing parts 1020 a and 1020 b are fixedly securedtogether by a mechanical joint system where part-to-part attachment isaccomplished with locating and locking features. In one embodiment,housing parts 1020 a and 1020 b are fixedly secured using clips wheresaid clips can be integral to one or the other or both housing parts. Inanother embodiment, securing clips are separate from housing parts 1020a and 1020 b. In one embodiment, housing 102 is generally elliptical intransverse cross-section to accommodate dosage mechanism 126. In oneembodiment, the generally elliptical housing 102 is configured withgenerally flat surfaces opposing one another on said housing. In oneembodiment, housing 102 is configured with flat surfaces sufficient tominimize the potential for the device to roll. In one embodiment, theflat surfaces found as part of elliptical housing 102 are designed toretain internal device components. In one embodiment, the flat surfacesof elliptical housing 102 are designed to retain dosing mechanism 126.In one embodiment, the flat surfaces for housing 102 contain rails andribs for retaining internal device components. In one embodiment,housing 102 is provided with an external thread or another suitableconnections means at a distal portion of the housing 102 to releasablyconnect a cartridge sleeve 114 thereto. In one embodiment, housing 102is provided with suitable connection means at a distal portion ofhousing 102 to adjustably connect the cartridge sleeve 114 thereto.

In one embodiment, injection device distal section 122 includes acartridge sleeve 114 which can be used to hold a number ofdifferently-sized cartridges. Additionally, a number ofdifferently-sized cartridge sleeves can be provided, as necessary fordifferently-sized cartridges. In one embodiment, the cartridge sleeve114 is provided with an internal thread or another suitable connectionsmeans at a proximal portion of the cartridge sleeve 114 to releasablyconnect housing 102 thereto. In one embodiment, cartridge sleeve 114 isprovided with suitable connection means at its proximal end toadjustably connect the cartridge sleeve 114 to housing 102 thereto. Inone embodiment, the cartridge sleeve 114 is reversibly connected tohousing 102. In one embodiment, the reversible connection of cartridgesleeve 114 to housing 102 allows replacement of medicament cartridge 112and re-setting of device 114.

In one embodiment, cartridge sleeve 114 is provided with an externalthread 118 or another suitable connections means 118 at a distal portionof cartridge sleeve 114 to releasably connect a pen-needle assemblythereto.

In one embodiment, a pen-needle assembly (not shown) is of known designand includes a double-ended needle cannula or injection needle. In oneembodiment, the pen-needle assembly consists of an injection needlemounted in a tubular hub that is internally threaded to cooperate withthe external thread 118 of cartridge sleeve 114 so as to be reversiblyattached to the external threading of the cartridge sleeve 114. Othertypes of connection types, including a snap on connection, may beprovided between the needle assembly and the cartridge sleeve 114. Inone embodiment, the injection needle is fitted with a protective cover,e.g, a needle cap, thereover to protect those handling or who mayotherwise encounter injection device 100. In one embodiment, thepen-needle assembly is a single injection needle. Various types of otherneedle assemblies known in the art may be used with injection device100, including, but not limited to, assemblies with one or moreshortened injection needles, including microneedle arrays, pen needleassemblies incorporating sharps protection or assemblies compatible withor connectable to intravenous lines or the like including needle-freeblunt connections.

In one embodiment, injection device 100 includes a cartridge 112. In oneembodiment, cartridge 112 is of the type typically used in connectionwith injection devices, e.g., needled injector devices, and is formed ofglass or certain types of plastic that have qualities that are necessaryfor storage of liquid medicament. Such qualities can include low airpermeation, lubricity, low leeching of chemicals and corrosionresistance. In one embodiment, cartridge 112 is generally cylindrical inshape and can have a diameter configured to fit within cartridge sleeve114, although other shapes can be used. In one embodiment, cartridge 112and cartridge sleeve 114 are engage at an interface. In one embodiment,an adhesive is applied at the interface of cartridge 112 and cartridgesleeve 114. In one embodiment, the adhesive is light cured. In oneembodiment, the cartridge 112 defines a medicament-filled reservoir thatis closed at its proximal end by a plunger 110 that is axially slideablyand sealably engaged with the cartridge interior wall to hold themedicament within the reservoir. In one embodiment, the distal, outletend of the cartridge reservoir is sealed by a septum held by a cap thatis secured to a stepped-down diameter neck portion of the cartridge 112.In one embodiment, the septum cap secured to the stepped-down diameterneck of the cartridge 112 is secured in the stepped down distal end ofthe cartridge sleeve 114 around which external threads 118 are present.In one embodiment, when the pen-needle assembly is mounted on cartridgesleeve 114, a proximal point of an injection needle penetrates thecartridge septum to provide a fluid flow outlet by which medicamentwithin the cartridge reservoir can be dispensed from a needle tip duringoperations of injection device 100. In one embodiment, cartridge 112 isconfigured to contain a predetermined amount of a medicament. Thepredetermined amount of medicament that the cartridge is configured tocontain can vary with the medicament injected and with the recommendeddose size for the particular medicament and the patient. In oneembodiment, distally advancing plunger 110 causes the volume of thecartridge reservoir to decrease and an amount of liquid medicament toexpel from the injection needle in an amount that corresponds to thereduction in volume caused by the movement of the plunger.

To reliably provide repeated small doses of a liquid medicament, in oneembodiment, cartridge 112 is constructed to hold a predetermined numberof doses. In one embodiment, the doses in cartridge 112 correspond to apredetermined period of medicament administration. In one embodiment,cartridge 112 is constructed to hold a predetermined volume ofmedicament. In one embodiment, the doses in cartridge 112 includesufficient medicament for purging air from the cartridge 112 andmedicament to correspond to a predetermined period of medicamentadministration. In one embodiment, the medicament in the cartridge issufficient for purging air from the cartridge, allow for practiceinjections, correspond to a predetermined period of medicamentadministration and allow for residual medicament assuring the last doseof medicament is a complete dose. For example, in one embodiment,injector device 100 is intended for use with a teriparatide solutionthat is to be administered once daily and sufficient drug is providedfor the prescribed treatment over a pre-determined number of successivedays at a dose of 0.08 mL administered through movement of a plunger 110a distance of about 1.1 mm. For example, in one embodiment, injectordevice 100 is intended for use with a teriparatide solution that is tobe administered once daily for twenty eight successive days at a dose of0.08 mL administered through movement of a plunger 110 a distance ofabout 1.1 mm. In one embodiment, the injector device 100 is configuredto administer a dose of medicament, e.g., teriparatide, once daily for 1day, 2 successive days, 3 successive days, 4 successive days, 5successive days, 6 successive days, 7 successive days, 8 successivedays, 9 successive days, 10 successive days, 11 successive days, 12successive days, 13 successive days, 14 successive days, 15 successivedays, 16 successive days, 17 successive days, 18 successive days, 19successive days, 20 successive days, 21 successive days, 22 successivedays, 23 successive days, 24 successive days, 25 successive days, 26successive days, 27 successive days, 28 successive days, 29 successivedays, 30 successive days, 31 successive days, 32 successive days, 33successive days, 34 successive days, 35 successive days, 36 successivedays, 37 successive days, 38 successive days, 39 successive days, 40successive days, or any range determinable from the preceding days (forexample, 3 successive days to 5 successive days or 25 successive days to35 successive days).

In one embodiment, cartridge 112 is configured to contain about 3 mL ofteriparatide. In one embodiment, cartridge 112 is configured to containabout 2.7 mL of teriparatide. In one embodiment, cartridge has adiameter of about 12 mm and a height of approximately 64 mm to contain 3mL of medicament, although other dimensions can be used to achieve thedesired accuracy. In another embodiment, cartridge 112 has a diameter ofabout 12 mm and a height of approximately 64 mm to contain about 2.7 mLof medicament, although other dimensions can be used to achieve thedesired accuracy. Cartridges 112 containing more or less medicament canbe provided and can vary in diameter, height or both. In one embodiment,cartridge 112 is configured to hold between about 0.5 mL, 1.0 mL, about1.5 mL, about 2.0 mL, about 2.5 mL, about 3.0 mL, about 3.5 mL, about4.0 mL, about 4.5 mL, about 5.0 mL, about 5.5 mL, about 6.0 mL, about6.5 mL, about 7.0 mL, about 7.5 mL, about 8.0 mL, about 8.5 mL, about9.0 mL, about 9.5 mL, about 10.0 mL or any range determinable from thepreceding amounts (for example, about 2 mL to about 5 mL or 3.0 mL toabout 9.5 mL) of liquid medicament. In one embodiment, injection device100 is configured to dispense different amounts of liquid medicament perdose. Further, the overall volume can be increased to include apredetermined amount of additional volume that remains in cartridge 112when the intended dosing is complete. This can reduce the likelihood ofan incomplete final dose or the presence of air in an injection.

With additional reference to FIGS. 1B, 1C, 3A and 3B, 15A, 15B, 17A and17B, proximal section 120 of injection device 100 contains the dosagemechanism 126 which is configured to cause movement of plunger 110contained in cartridge 112 a predetermined dosing distance. Thismovement may occur in successive increments and such successiveincrements may correspond to the number of doses to be administered. Inone embodiment, dosage mechanism 126 includes a ram 108, a ratchet gear116, a crank arm 106 and a user-manipulable push button 104.

Referring to FIGS. 4 and 18 , in one embodiment, ram 108 has a foot1084, a shaft 1086, and a support bar 1088. In one embodiment, foot 1084is at a distal end of shaft 1086 and includes a planar surface. In oneembodiment, the planar surface is circular. In one embodiment, foot 1084has a larger surface area than any transverse cross-sectional area ofthe shaft 1086 to distribute loading on the cartridge plunger 110 thatfoot 1084 contacts and thereby directly engages cartridge plunger 110during advancement. In one embodiment, shaft 1086 has a distal portion1090 having a larger transverse cross-sectional area than a transversecross-sectional area of a proximal portion 1092 to distribute loading onthe foot 1084. In one embodiment, shaft 1086 is not axially aligned withthe center of foot 1084. In one embodiment, ram 108 includes a lock outprotrusion 1094 (as shown in FIG. 4 ) or a lock out protrusion 1096 (asshown in FIGS. 13A, 13B, and 18 ) that extends from a proximal end ofshaft 1086 configured for use with a lock-out feature (described in moredetail below). In one embodiment, shaft 1086 has at least two sets ofteeth, gear engaging teeth 1080 and pawl engaging teeth 1082 axiallydisposed along opposing sides of a portion of shaft 1086. In oneembodiment, the geometry of gear engaging teeth 1080 matches thegeometry of pinion teeth 1162 on ratchet gear 116 (discussed in moredetail below). The pawl engaging teeth 1082 are spaced apart linearlyaccording to the dose travel amount. In one embodiment, pawl engagingteeth 1082 include a pressure angle. In one embodiment, the pressureangle of pawl engaging teeth 1082 is axially aligned with the plungeraxis. In another embodiment, support bar 1088 is axially disposed alonga portion of shaft 1086. In another embodiment support bar 1088 isconfigured to interact with second portion of housing 1020 b In anotherembodiment, support bar 1088 is on shaft 1086 to provide stiffness tothe part.

Referring to FIGS. 5 and 19 , in one embodiment, ram 108 is constrainedby the internal shaping of the housing 102 to be axially translatableand rotatably fixed therein. As shown in FIGS. 2B and 16B, in oneembodiment, second portion of housing 1020 b has a support bar receivingslot 1028 which is configured to hold support bar 1088 of ram 108 toprevent rotation and allow axial translation of the ram 108. In certainembodiments, lateral or rotational ram movement disengages the pinionteeth 1162. In one embodiment, ram 108 is movable in the distaldirection and prevented from proximal movement relative to the housing102. As shown in FIGS. 5 and 19 , in one embodiment, pawl engaging teeth1082 are employed with a portion of housing 102 to provide for theseone-way axial motions.

In one embodiment, pawl engaging teeth 1082 are provided with a one-wayramping, and are engageable with a pawl 1026, which is integrally formedwithin in the second portion of housing 1020 b and functions withinhousing 102. In one embodiment, ram teeth 1082 slide over pawl 1026 asthe ram 108 is moved distally during injection, but pawl 1026 abuts pawlengaging teeth 1082 upon proximal movement of ram 108. In oneembodiment, pawl 1026 is in interference with and presses ram 108 suchthat gear engaging teeth 1080 are in close contact with pinion teeth1162. In one embodiment, pawl engaging teeth 1082 are equal in length,resulting in ram travel being of equal length per stroke and resultingin a single or fixed dose injection device. In a multiple dose, fixeddose embodiment, pawl engaging teeth 1082 are of unequal in length,resulting in unequal ram travel per stroke.

Referring to FIGS. 3B and 17B, in one embodiment, gear engaging teeth1080 are engageable with ratchet gear 116. In one embodiment, pinionteeth 1162 and ratchet teeth 1164 are in one component connected throughaxis 1160. In one embodiment, the ratchet teeth 1164 are spaced at apredetermined angle. In one embodiment, the pinion teeth 1162 have apredetermined pitch diameter and involute gear teeth geometry. In oneembodiment, the combination of the angular rotation of the ratchet gear116, the pinion teeth 1162 and the gear engaging teeth 1080 on the ram108 control the dosage amount. Ram 108 is shown in FIGS. 4 and 18 asbeing integrally provided with its gear engaging teeth 1080 and pawlengaging teeth 1082, such as by being made of a one-piece plasticinjection molding, or a one-piece metal part. Other constructions of ram108, such as an assembly of separately formed component parts, arewithin the scope of the invention.

Referring to FIGS. 3A, 3B, 17A and 17B, in one embodiment, the dosagemechanism 126 includes a ratchet gear 116. In one embodiment, ratchetgear 116 is centered longitudinally within injection device 100. In oneembodiment, ratchet gear 116 is not centered longitudinally withininjection device 100. As shown in FIG. 6 , in one embodiment, ratchetgear 116 includes housing engagement members 1166 a and 1166 b and twosets of gear teeth, pinion teeth 1162 and ratchet gear teeth 1164. Inone embodiment, housing engagement member 1166 a defines an axis 1160for rolling rotation of ratchet gear 116. In one embodiment, as shown inFIG. 20 , ratchet gear 116 includes a recess 1168 (rather than housingengagement member 1166 b), which is configured to couple with housingmating pin 1024 c (as shown in FIG. 16B) disposed on the internalsurface of house part 1020 b to aid in preventing axial translation andallowing rotation of the ratchet gear about axis 1160. In oneembodiment, axis 1160 is perpendicular to axis 124. In one embodiment,ratchet gear 116 is constrained by the internal shaping of the housing102 to be rotatable about axis 1160 and axial fixed therein. In oneembodiment, housing parts 1020 a and 1020 b have ratchet gear engagementmembers 1024 a and 1024 b which are configured to engage housingengagement members 1166 a and 1166 b of ratchet gear 116, respectively,to prevent axial translation and allow rotation of the ratchet gearabout axis 1160. In one embodiment, ratchet gear 116 includes housingengagement members 1166 a and 1166 b configured to engage protrusions ofhousing parts 1020 a and 1020 b, such configuration preventing axialtranslation and allowing rotation of the ratchet gear about axis 1160.

Referring to FIGS. 1B and 15A, in one embodiment, pinion teeth 1162 area continuous ring of teeth that are configured to engage gear engagingteeth 1080 of ram 108 such that as ratchet gear 116 rotates about axis1160, ram 108 axially advances. In one embodiment, the ratchet gearteeth 1164 are a continuous ring of teeth that are configured to engagea crank arm 106. In one embodiment, ratchet gear teeth 1164 have one-wayramping. In one embodiment, the diameter of pinion teeth 1162 is smallerthan the diameter of ratchet gear teeth 1164. In one embodiment, thenumber of teeth in pinion teeth 1162 is less than the number of teeth inratchet gear teeth 1164. In one embodiment, there are 15 pinion teeth1162. In another embodiment, there are 20 ratchet gear teeth 1164.Although pinion teeth 1162 and ratchet teeth 1164 are shown integrallyformed in FIG. 6 , these components can be separately formed andassembled together so as to be co-rotatable. In one embodiment, ratchetgear 116 moves forward by turning counterclockwise to dispensemedicament. In another embodiment, ratchet gear 116 moves forward byturning clockwise to dispense medicament. As shown in FIG. 15B, in oneembodiment, ratchet gear 116 includes a ratchet gear marker 1168. In oneembodiment, alignment of ratchet gear marker 1168 with a protrusion 1030on either of housing parts 1020 a or 1020 b prior to a first use ofinjection device 100 ensures that dosage mechanism 126 is in a properpre-fired orientation. In one embodiment, protrusion 1030 preventsratchet gear 116 from turning backwards by only allowing ratchet teeth1164 to ramp over housing protrusion 1030.

Referring to FIGS. 3A, 3B, 7, 17A, 17B, and 21 , in one embodiment, thedosage mechanism 126 includes a crank arm 106. In one embodiment, asshown in FIGS. 7 and 21 , crank arm 106 is generally V-shaped, havingtwo legs, a crank arm leg 1066 and a pawl arm leg 1068. In oneembodiment, crank arm leg 1066 includes a crank arm pivot hole 1064 atdistal end which is configured to be slideably engageable with housingengagement member 1166 a of the ratchet gear 116, which allows the crankarm 106 to be rotatable about axis 1160 but be axially fixed. In oneembodiment, the crank arm pivot hole 1064 is generally aligned with axis1160. In one embodiment, pawl arm leg 1068 includes a pawl tooth 1062which is shaped to mesh with ratchet teeth 1164. In one embodiment,crank arm 106 includes a push button engagement member 1060, e.g., aprojection, at the apex of crank arm 106 that extends from the apextowards slot 1046 b on push button 104. In one embodiment, push buttonengagement member 1060 is configured to be slideably engageable withslot 1064 b. In one embodiment, axially distal movement of push button104 relative to housing 102 causes crank arm 106 to rotate about axis1160 and pawl tooth 1062 to engage ratchet gear teeth 1164, causingratchet gear 116 to rotate pinion teeth 1162 about axis 1160 that causesram 108 to distally advance. In one embodiment, axially proximalmovement of push button 104 relative to the housing 102 causes crank arm106 to rotate about axis 1160 in an opposite direction and pawl tooth1062 to disengage ratchet gear teeth 1164.

With continued reference to FIGS. 3A, 3B, 17A and 17B, in oneembodiment, the dosage mechanism 126 includes a user-manipulable pushbutton 104 that allows the user to actuate the injection device 100. Inone embodiment, as shown in FIG. 8 , push button 104 is a unitarystructure. In one embodiment, as shown in FIGS. 9A, 9B, and 9C, pushbutton 104 is a non-unitary structure. In one embodiment, as shown inFIGS. 9A, 9B and 9C, push button 104 includes a cap 1040, a connector1042, a force limiting biasing member 1044, and a base member 1046. Inone embodiment, cap 1040 includes a user-contacting portion 1040 a andtabs 1040 b. In one embodiment, user-contacting portion 1040 a has ahollow portion configured to facilitate connection with connector 1042.In one embodiment, tabs 1040 b are configured to snap fit withcorresponding features of connector 1042. In one embodiment, cap 1040 ismolded from plastic. In other embodiments, cap 1040 a is covered with asoft touch material. In one embodiment, tabs 1040 b are sized and shapedto be fixed within connector 1042. In one embodiment, cap 1040 andconnector 1042 are different colors. In one embodiment, when injectiondevice 100 is in the fired state, connector 1042 is not visible. In oneembodiment, when injection device 100 is not in a fired state, theconnector 1042 is visible. In one embodiment, cap 1040 and connector1042 are different colors so that a user can visually determine whetherinjection device 100 is in a fired state or not in a fired state.

Referring to FIGS. 9A, 9B and 9C, in one embodiment, connector 1042 ofpush button 104 includes connector body 1042 a having a hollow portion1042 b, tabs 1042 c, and a linear travel guide 1042 f. In anotherembodiment, connector 1042 of push button 104 includes connector body1042 a having an indicating band 1042 e. In one embodiment, tabs 1042 cproximally extend from connector body 1042 a. In another embodiment,tabs 1042 c are sized and shaped to facilitate a fixed connectionbetween cap 1040 and connector 1042. Cap 1040 and connector 1042 areshown as being fixedly connected via the use of tabs in FIG. 8 . Inother embodiments, cap 1040 and connector 1042 are integrally formed,such as by being made of a one-piece plastic injection molding, or aone-piece metal part.

In another embodiment, a linear travel guide 1042 f extends from adistal portion of the connector body 1042 a. In one embodiment, lineartravel guide 1042 f is configured to limit withdrawal of the push buttonfrom housing 102 and insertion of the push button into housing 102. Inone embodiment, linear travel guide 1042 f includes a shelf 1042 dconfigured to engage housing 102 to limit withdrawal of the push buttonfrom housing 102. In one embodiment, linear travel guide 1042 f includesa guide base 1042 g configured to engage housing 102 to limit insertionof the push button into housing 102. In one embodiment, shelf 1042 d issized and shaped to engage with lip 1032 of housing 102 to limitwithdrawal of the push button 104 from housing 102. In otherembodiments, guide base 1042 g is sized and shaped to engage a baseengaging member 1034 of housing 102 to limit insertion of the pushbutton 104 into the housing. In other embodiments, the linear travelguide 1042 f is sized and shaped to slideably fit within shelf engagingopenings 1036 of housing 102 to limit both the withdrawal and insertionof push button 104 into and out of housing 102. In one embodiment,linear travel guide 1042 f is used to keep connector body 1042 alignedaxially with the housing parts 1020 a and 1020 b. As shown FIG. 8 , insome embodiments, the linear travel guide 1042 f extends continuouslyalong the circumference of the connector body 1042 a. As shown in FIGS.9A, 9B, and 9C, in other embodiments, linear travel guide 1042 f extendsdiscontinuously along the circumference of the connector body 1042 a. Inone embodiment, indicating band 1042 e is configured to be visible to auser when push button 104 has been properly withdrawn from the housing102 to prepare injection device 100 for medicament delivery. As shown inFIG. 8 , in one embodiment, indicating band 1042 e extends continuouslyalong the circumference of connector body 1042 a. As shown in FIGS. 9A,9B, and 9C, in other embodiments, indicating band 1042 e extendsdiscontinuously along the circumference of connector body 1042 a. In oneembodiment, indicating band 1042 e can incorporate a color, e.g., red,to add to the affect thereof. In one embodiment, when indicating band1042 e is visible, injection device 100 is in the ready (or reset)state. In one embodiment, when injecting band 1042 e is not visible,injection device 100 is in the fired state. In one embodiment, hollowportion 1042 b of connector body 1042 a is sized and shaped to holdforce limiting biasing member 1044.

In one embodiment, force limiting biasing member 1044 of push button 104is a metal, helically-coiled compression spring. In one embodiment,force limiting biasing member 1044 is disposed within hollow portion1042 b of connector body 1042 a. In one embodiment, force limitingbiasing member 1044 is captured in a pre-stressed force state betweenthe interior end of cap 1040 and a top portion of flanges 1046 a of basemember 1046 (described in more detail below). In one embodiment, thepre-stressing force is at minimum as large as forces users exert on thepush button during proper operation of injection device 100. In oneembodiment, the pre-stressing force is no larger than what the dosingmechanism 126 can withstand without damage to the interactingcomponents. Thus, in one embodiment, during normal actuation ofinjection device 100, force limiting biasing member 1044 does notfurther compress, as shown in FIGS. 10A, 10B, and 10C. FIGS. 10A, 10B,and 10C show an exemplary force limiting biasing member 1044 duringnormal operation of injection device 100. In another embodiment, asshown in FIGS. 11A, 11B, 11C, and 11D, force limiting biasing member1044 is designed with sufficient spacing in its coiling, and with properelastic properties, such that the force limiting biasing member 1044, bycompression, can accommodate movement of push button 104 from a ready(or reset) state to a fired stated without movement of ram 108, ratchetgear 116, or crank arm 106, whereby force limiting biasing member 1044can absorb actuation forces that could damage components. FIGS. 11A,11B, 11C, and 11D show an exemplary force limiting biasing member 1044compressing within connector 1042 which can occur when for example therea needle is miscoupled or occluded.

Referring to FIGS. 12A-12E, in one embodiment, injection device 100 hasa ready (or reset) state wherein push button 104 is withdrawn from thehousing 102 and indicator 1042 is visible to the user, as shown in FIG.12C. In another embodiment, injection device 100 has a fired statewherein push button 104 is actuated and the base rim of cap 1040 isflush against a top portion of the housing 102, as shown in FIGS. 12Aand 12E. In one embodiment, movement of push button 104 distally alongaxis 124 from a ready (or reset) state towards a fired state isconsidered firing motion, as shown in FIGS. 12C through 12E. Whereas, inanother embodiment, movement of push button 104 proximally along axis124 from a fired state towards a ready (or reset) state is consideredresetting motion, as shown in FIGS. 12A through 12C.

Referring to FIG. 8 , in one embodiment, base member 1046 includes alockout aperture 1046 g configured for use with a lock-out feature(described in more detail below). In one embodiment, base member 1046 ofpush button 104 includes flanges 1046 a that are configured to beslideably connected within the hollow portion 1042 b of connector 1042.In one embodiment, flanges 1046 a are configured to be slideablyconnected to tracks disposed within the hollow portion 1042 b ofconnector 1042 to ensure axial alignment of base member 1046 andconnector 1042. In certain embodiments, the connection of flanges 1046 aand the hollow portion 1042 b of connector 1042 are such that basemember 1046 is restricted to sliding generally axially along theinterior surface of the hollow portion 1042 and such that the basemember 1046 is restricted from generally rotating about the interiorsurface of the hollow portion 1042. In one embodiment, base member 1046and housing 1020 b are integrally connected to restrict movement of pushbutton 104 to linear movements along axis 124. In certain embodiments,base member 1046 is configured to engage housing 102 to restrictmovement of push button 104 to linear movement along axis 124. Incertain embodiments, as shown in FIGS. 16B and 17B, base member 1046 hashousing engagement slots 1046 e that engage base member engagementplates 1021 of housing 1020 b to restrict movement of push button 104 tolinear movement along axis 124. As shown in FIG. 8 , in anotherembodiment, base member 1046 has a housing engagement protrusion 1046 fthat is configured to engage base member engagement slot 1038 of housing1020 b to restrict movement of push button 104 to linear movements alongaxis 124.

Referring to FIG. 3B, in one embodiment, base member 1046 includes aslot 1046 b disposed through the base member 1046. In one embodiment,slot 1046 b is configured to engage push button engagement member 1060of crank arm 106. In one embodiment, slot 1046 b is slideably engageablewith push button engagement member 1060. In one embodiment, slot 1046 bis generally rectangular shaped. In another embodiment, slot 1046 b isgenerally rectangular shaped with curved ends. In another embodiment,slot 1046 b is generally polygonal. in another embodiment, slot 1046 iscurved. In one embodiment, slot 1046 b is oriented at an oblique anglewith respect to axis 124. In one embodiment, translation of push button104 distally or proximally along axis 124 causes push button engagementmember 1060 to translate along the path of slot 1046 b. In oneembodiment, translation of push button 104 from a ready (or reset) statedistally along axis 124 causes push button engagement member 1060 totranslate along the path of slot 1046 b, causing crank arm 106 to rotateabout axis 1160. The path traced by slot 1046 b could be of any geometrythat crank arm engagement member 1060 could travel in. While keeping thestart position and end position of this slot the same, a fixed dose canbe achieved while varying the button force profile exerted by the user.

Referring to FIG. 9A, in one embodiment, slot 1046 b of base member 1046has portion 1046 i and portion 1046 j. In one embodiment, portion 1046 iand portion 1046 j of slot 1046 b are at different angles with respectto axis 124. In one embodiment, portion 1046 i is oriented at an obliqueangle with respect to axis 124. In another embodiment, portion 1046 j isoriented parallel to axis 124. In one embodiment, slot portion 1046 jallows a user to translate push button 104 from a ready (or reset) statedistally along axis 124 for a distance without movement of any othercomponents of dosing mechanism 126. In one embodiment, translation ofpush button 104 distally along axis 124 from a ready (or reset) statetranslates push button engagement member 1060 (FIG. 7 ) along the pathof slot portion 1046 j, which keeps crank arm 106 from rotating aboutaxis 1160 (FIG. 3B). In one embodiment, when push button engagementmember 1060 is positioned at the most distal portion of slot portion1046 i, further translation of push button 104 distally along axis 124translates push button engagement member 1060 along the path of slot1046 i, causing crank arm 106 to rotate about axis 1160. In oneembodiment, the orientation of slot portion 1046 j allows a user topress push button 104 for a period of time without injecting anymedicament. In another embodiment, slot portion 1046 i could have thesame orientation with the same effect that push button 104 is pushedwithout the injection of medicament. The slot portion 1046 j allows theuser to build up momentum of push button 104 prior to injection of amedicament dose. Injection of medicament into a user can often timecause discomfort to the user, which can cause the user to withdraw theinjection needle prior to full medicament dose injection. In oneembodiment, the momentum of push button 104 that is built up as the userpresses push button without injection of medicament is sufficient toallow for injection of a medicament dose with sufficient speed as to notprovide the user time to react to any discomfort from medicamentinjection and withdraw the injection needle prior to full medicamentdose injection. In another embodiment, the geometry of 1046 j would havea vertical portion on the proximal end. In other embodiments, slotangles with longer or shorter sections alike 1046 j or curved orparabolic slot would have changing force profiles of the button. In oneembodiment a straight linear slot is implemented to keep constant forceand contact with crank arm engagement member. In one embodiment, with alinear slot, the angle produced by the slot is a product of twodimensions. The vertical dimension, which stretches from the distalportion of the slot to the proximal portion of the slot and parallel toproximal-distal axis 124, is correlated to the desired button stroke.The horizontal dimension, perpendicular to proximal-distal axis 124 andstretching from the two furthest points on the slot directly correlateto the rotation of the crank arm 106.

In one embodiment, base member 1046 includes a flexible column 1046 cextending proximally from a distal portion of base member 1046. In otherembodiments, a column tooth 1046 d extends perpendicularly from aproximal portion of flexible column 1046 c. In certain embodiments,column tooth 1046 d is generally almond shaped, as shown in FIG. 9A. Inother embodiments, column tooth 1046 d is generally cylindricallyshaped, as shown in FIG. 8 . In other embodiments, column tooth 1046 dis generally polyhedronally shaped. Other shapes of column teeth 1046 dare within the scope of this invention. In one embodiment, as shown inFIGS. 1B and 1C, column tooth 1046 d is configured to engage theanti-retrograde ratchet side 1022 b of unidirectional rack 1022. In oneembodiment, a unidirectional rack 1022 is integrally formed on theinternal surfaces of housing parts 1020 a and 1020 b. In oneconfiguration, column tooth 1046 d can be found in a double shear typeload, which is known to be stronger and more stable than single shearconfigurations. In another embodiment, unidirectional rack 1022 isformed on the internal surface of only of housing parts 1020 a and 1020b, placing unidirectional rack 1022 and column tooth 1046 d in a singleshear configuration.

In one embodiment, unidirectional rack 1022 has a smooth linear ratchetside 1022 a and an anti-retrograde ratchet side 1022 b. In oneembodiment, the anti-retrograde ratcheted side 1022 b of unidirectionalrack 1022 is configured to engage column tooth 1046 d and only allowmovement of push button 104 in one direction, e.g., from the fired stateto the ready (or reset) state. In certain embodiments, theanti-retrograde ratchet side 1022 b of unidirectional rack 1022 hascurved surfaces at both a proximal end and a distal end. In oneembodiment, the proximal curved surface of anti-retrograde ratchet side1022 b is configured to bias the flexible column in a way to forcecolumn tooth 1046 d to the smooth linear ratchet side 1022 a of theunidirectional rack 1022. In one embodiment, the distal curved surfaceof anti-retrograde ratchet side 1022 b is configured to bias theflexible column 1046 c in a way to force column tooth 1046 d to theanti-retrograde ratchet side 1022 b of unidirectional rack 1022. In oneembodiment, during resetting motion of push button 104, protrusions 1046d engage the distal curved surfaces of unidirectional rack 1022 causingflexible column 1046 to bias and forcing protrusions 1046 d to theanti-retrograde ratchet side 1022 b of unidirectional rack 1022, asshown in FIGS. 12A and 12B. In certain embodiments, if push button 104is moved in a distal direction prior to completion of the resettingmotion, protrusions 1046 d would engage the ratchets of anti-retrograderatchet side 1022 b of unidirectional rack 1022, preventing distalmovement. In one embodiment, during firing motion of push button 104,protrusions 1046 d engage the proximal curved surfaces ofanti-retrograde ratchet side 1022 b of unidirectional rack 1022, causingflexible column 1046 to bias and forcing column tooth 1046 d to thesmooth linear ratchet side 1022 a of unidirectional rack 1022, as shownin FIGS. 12C and 12D. In certain embodiments, the column tooth 1046 dslides along the smooth linear ratchet side 1022 a of unidirectionalrack 1022 until the device is in the fired state. In one embodiment, thefull amount of medicament which is to be expelled during the firingmotion is only fully expelled upon push button 104 reaching the firedstate. In one embodiment, if the push button does not complete thefiring motion, the full amount of medicament for that dose is not fullyexpelled. In certain embodiments, a successive dose cannot beeffectuated until the previous dosage amount of medicament is fullyexpelled. In one embodiment, the combination of the flexible column 1046c, column tooth 1046 d and anti-retrograde ratchet side 1022 b ofunidirectional rack 1022 are considered the anti-reverse feature. Inanother embodiment, the combination of the interactions between theflexible column 1046 c, column tooth 1046 d and anti-retrograde ratchetside 1022 b of unidirectional rack 1022, and the engagement of pawl 1026of the housing 1020 b with pawl engaging teeth 1082 are considered theanti-reverse feature.

Referring to FIG. 1C, in certain embodiments, the dosing mechanism 126includes a lock-out feature, e.g., prevention of push button 104 fromresetting from its fired position upon completion of the allottedmedicament doses. In one embodiment, as shown in FIGS. 3A and 3B, thelock-out feature includes a protrusion 1094, which extends from aproximal portion of ram shaft 1086 in an opposite direction of supportbar 1088 (FIG. 4 ), and a lockout aperture 1046 g disposed in the basemember 1046 of push button 104 (FIG. 8 ). In one embodiment, lockoutaperture 1046 g is disposed above slot 1046 b. In one embodiment,protrusion 1094 is sized and shaped to protrude into lockout aperture1046 g. In one embodiment, lockout aperture 1046 g is of a complimentaryshape of protrusion 1094. In one embodiment, after each firing of theinjection device 100, ram 108 is translated distally relative to thehousing. In one embodiment, ram 108 is prevented from moving proximallyrelative to the housing because of engagement of pawl 1026 of thehousing with pawl engaging teeth 1082. In one embodiment, after thefinal dose of medicament is expelled from the injection device, ramshaft 1086 is sufficiently distally translated so that when push button104 reaches the fired state, protrusion 1094 and lockout aperture 1046 gare aligned. In one embodiment, protrusion 1094 slides into lockoutaperture 1046 g thereby restricting movement of push button 104, e.g.,push button 104 cannot reset because it is connected to ram shaft 1086which is prevented from moving proximally relative to the housing bypawl 1026. In one embodiment, the proximal surface of protrusion 1094 isdesigned to promote protrusion 1094 sliding into lock out aperture 1046g. In one embodiment, the distal surface of protrusion 1094 is designedto remain engaged with the proximal surface of lockout aperture 1046 g.

Referring to FIGS. 13A and 13B, in another embodiment, the lock-outfeature includes a protrusion 1096 (as shown in FIG. 18 ), which extendsfrom a proximal portion of ram shaft 1086, a lock-out member 2000integrally formed within housing part 1020 b, and a flange 1046 hextending from base member 1046 towards housing 1020 b. In oneembodiment, lock-out member 2000 is only attached to the housing via ahousing cross plate at a distal end of the lock-out member 2000. In oneembodiment, lock-out member 2000 is flexible. In one embodiment,lock-out member 2000 includes a lockout deflector 2000 a and a hook 2000b. In one embodiment, lockout deflector 2000 a of lock-out member 2000is centrally positioned on the lock-out member 2000. In one embodiment,lockout deflector 2000 a of lock-out member 2000 is configured to engageprotrusion 1096 of ram 108. In one embodiment, lockout deflector 2000 aof lockout member 2000 is configured to slidingly engage protrusion 1096of ram 108. In one embodiment, hook 2000 b of lock-out member 2000 ispositioned at a proximal end of lock-out member 2000. In anotherembodiment, hook 2000 b is configured to engage flange 1046 h of basemember 1046. As shown in FIGS. 13A and 13B, in one embodiment, duringthe firing motion of push button 104 of the final medicament dose of theinjection device 100, protrusion 1096 of ram 108 engages lockoutdeflector 2000 a of lock-out member 2000. In one embodiment, engagementof protrusion 1096 and lockout deflector 2000 a biases lock-out member2000 such that hook 2000 b extends into the path of flange 1046 h. Asshown in FIGS. 13C and 13D, in one embodiment, once hook extends intothe path of flange 1046 h, any attempted resetting motion of push button104 would cause engagement of hook 2000 b and flange 1046 h. In oneembodiment, engagement of hook 2000 b and flange 1046 h prevent anyresetting motion of push button 104, thus, locking out the device fromfurther use. In one embodiment, a portion of housing part 1020 b is cutout in the shape of lock-out member 2000. The cut out portion of housingpart 1020 b is aligned with lock-out member 2000 so as to give a visualindication that the lock-out feature has been activated. In oneembodiment, injection device 100 includes a cover 130 engagable withhousing 102 that removably covers the cut out portion of housing part1020 b.

While the dosing mechanism described herein is shown as a part of aneedled injection device for a liquid medicament, it is understood thatthe mechanism can be used in other dispensing devices that include adispenser that is actuated by linear motion. This includes injectiondevices that use a mechanism other than a push button as well as otherdispensing devices for gels or the like which may or may not contain amedicament.

In one embodiment, the dose size can be varied by changing the diameterof cartridge 112. In certain embodiments, a higher diameter willincrease the dose size. In other embodiments, a smaller diameter willdecrease the dose size. In one embodiment, varying the space betweenpawl engaging teeth 1082 and, correspondingly, pinion teeth 1162, canvary the dose size. In other embodiments, varying the shape of crank arm106, the length of the crank arm leg 1066 or pawl arm leg 1068, or theangle of slot 1046 b of base member 1046 can vary the dose size byvarying the rotational angle of ratchet gear 116 caused by crank arm106. These factors can be adjusted to derive an injector that contains adesired amount of liquid medicament and will produce the desired numberof doses at a desired amount, and in certain embodiments fixed amount,and will have the desired dosing and resetting motions.

Each and every reference identified herein is incorporated by referencein its entirety. The entire disclosure of U.S. patent applicationpublication number 2010/0036320 is hereby incorporated herein byreference thereto as if fully set forth herein. The term “about,” asused herein, should generally be understood to refer to both thecorresponding number and a range of numbers. Moreover, all numericalranges herein should be understood to include each whole integer withinthe range.

It is to be understood that at least some of the figures anddescriptions of the invention have been simplified to focus on elementsthat are relevant for a clear understanding of the invention, whileeliminating, for purposes of clarity, other elements that those ofordinary skill in the art will appreciate may also comprise a portion ofthe invention. However, because such elements are well known in the art,and because they do not necessarily facilitate a better understanding ofthe invention, a description of such elements is not provided herein.

The invention claimed is:
 1. A dispensing mechanism, comprising: ahousing having a proximal-distal axis; a ram within the housing, movablein a distal direction relative to the housing; a push button moveablealong the proximal-distal axis relative to the housing, the push buttonincluding a push button slot at a distal portion of the push button; acrank arm having a pawl tooth, a pivot point, and a crank arm engagementmember slideably engageable with the push button slot such that movementof the push button causes the crank arm engagement member to move alongthe push button slot, causing rotation of the crank arm about the pivotpoint; and a ratchet gear having a first set of teeth releasablyengageable with the pawl tooth and a second set of teeth releasablyengageable with the ram, wherein engagement of the pawl tooth with thefirst set of teeth of the ratchet gear causes the ratchet gear torotate, causing the ram to distally advance relative to the housing, andwherein the ram includes a lockout protrusion and the push buttonincludes a lockout aperture, the lockout aperture engaging with thelockout protrusion in a locked position.
 2. The dispensing mechanism ofclaim 1, further comprising an anti-reverse mechanism including: atleast one housing ratchet integrally formed on an internal surface ofthe housing; and a flexible column integrally formed extending from adistal portion of the push button, the flexible column having a flexiblecolumn protrusion at a proximal end thereof, wherein as the push buttonmoves along the proximal-distal axis, the flexible column protrusionengages the housing ratchet and restricts movement of the push button toone direction during a resetting motion.
 3. The dispensing mechanism ofclaim 2, wherein the flexible column protrusion is almond shaped.
 4. Thedispensing mechanism of claim 1, wherein the ram includes at least twosets of teeth.
 5. The dispensing mechanism of claim 4, wherein at leastone set of teeth has involute spur rack geometry.
 6. The dispensingmechanism of claim 4, wherein a first set of ram teeth are configured toengage the second set of teeth of the ratchet gear, and a second set ofram teeth are configured to engage a housing protrusion, the housingprotrusion being integrally formed within the housing and configured tofacilitate movement of the ram in one direction.
 7. The dispensingmechanism of claim 6, wherein the first set of ram teeth and the secondset of teeth of the ratchet gear have similar corresponding involutegear teeth geometry.
 8. The dispensing mechanism of claim 1, wherein thepush button slot is oriented at an oblique angle with respect to theproximal-distal axis.
 9. The dispensing mechanism of claim 1, whereinthe push button slot has a portion that is oriented at an oblique anglewith respect to the proximal-distal axis and a portion that is orientedparallel to the proximal-distal axis.
 10. The dispensing mechanism ofclaim 1, wherein the first set of teeth of the ratchet gear control adose amount of an injector.
 11. An injector comprising: the dispensingmechanism of claim 1; a cartridge disposed within the housing; amedicament contained within the cartridge; a plunger disposed in thecartridge to seal the medicament therein, wherein the ram is associatedwith the plunger for forcing the plunger in a distal direction relativeto the housing for ejecting a dose of the medicament; and a needle influid communication with the cartridge for injecting doses of themedicament into a patient.
 12. The injector of claim 11, wherein themedicament includes a parathyroid hormone.
 13. The injector of claim 12,wherein the parathyroid hormone is teriparatide.
 14. The injector ofclaim 11, wherein the medicament includes glucagon-like peptide receptoragonists.
 15. The injector of claim 14, wherein the glucagon-likepeptide receptor agonists are exenatide.
 16. The injector of claim 14,wherein the glucagon-like peptide receptor agonists are liraglutide. 17.The dispensing mechanism of claim 1, wherein the lockout protrusionengages with the lockout aperture in the locked position after a dose ofa medicament is ejected.
 18. The dispensing mechanism of claim 1,wherein the lockout protrusion engages a sidewall of the lockoutaperture to restrict movement of the push button when the lockoutprotrusion is in the locked position.
 19. The dispensing mechanism ofclaim 18, wherein the lockout protrusion prevents proximal movement ofthe push button relative to the housing when the lockout protrusion isin the locked position.
 20. The dispensing mechanism of claim 1, whereinthe dispensing mechanism is configured to eject a plurality of doses ofa medicament including a final dose of the medicament and the lockoutprotrusion engages the lockout aperture in the locked position after thefinal dose of the medicament is ejected.
 21. The dispensing mechanism ofclaim 1, wherein the ram is prevented from moving proximally relative tothe housing in the locked position.